Download SLL_382010-3047_En

DRUG INFORMATION
EDITED BY: RISTO HUUPPONEN, JUHANA E. IDÄNPÄÄN-HEIKKILÄ, ANNIKKA KALLIOKOSKI, SAKARI
KARHUVAARA, ESA LEINONEN, JAANA PUHAKKA
MAARIT WUORELA
MD, Specialist in Nephrology,
Medicine, Geriatrics and
Clinical Microbiology, Senior
Physician, Turku City Hospital
TAPIO KUITUNEN
MD, Docent, Specialist in
Medicine, Nephrology and
Clinical Pharmacology,
administrative competence,
Medical Director, The Finnish
Defence Forces, Centre for
Military Medicine, Research
and Development Department
ARJA HELIN-SALMIVAARA
MD, Specialist in General
Practice, special qualification
in physician training, Director
of Physician Training, Senior
Researcher, HUS Unit of
General Practice and
University of Turku,
Department of Pharmacology,
Drug Development and
Therapeutics
Database to support decision-making concerning the pharmacotherapy
of patients with renal failure


The Renbase database provides support for selecting the appropriate drug and dosage for
patients with renal failure. The database was published in the Terveysportti health portal in
the autumn of 2009; it uses four-tier letter and colour coding to facilitate decision-making.
The database should be used whenever the patient’s renal function is not normal, or when
a new drug therapy is started for a patient over 65 years of age or the dosage is adjusted.
When a patient suffers from renal failure,
safe implementation of drug therapy may be
problematic in terms of selecting drugs and
finding a dosage that is appropriate in renal
failure. Renbase is available to most health
care professionals through Terveysportti
health portal and offers individualised,
dosage form-specific information to help
select the appropriate drug and dosage.
Renbase is a tool which is likely to improve
patient safety, expedite the physician’s work
and reduce the need for consultations.
Renbase can be used as part of Terveysportti
health portal’s drug database or separately
(drugs/kidneys). It is one of the chargeable services
provided by Terveysportti health portal. In the near
future, Renbase will also be linked to the decisionmaking support for The Finnish Medical Society
Duodecim and the main patient record systems
used in Finland to provide automatic warnings
concerning the implementation of drug therapy in
renal failure.
(Image from Renbase)
In addition to drugs available on the Finnish
market, the database also contains descriptive
safety information on vitamins, trace elements and
several medicinal products available for
compassionate use. There are a total of 1,009
classified substances with 3,934 references linked
to the Medline database. The recommendations in
the database are based on research reports that
have appeared in the indexed publication series of
the Medline database, and on American, Australian
and European summaries of product
characteristics. The recommendations are updated
monthly.
The database and the search
characteristics
In the user application, searches can be performed
either by generic drug name, ATC code or the trade
names of products. The Terveysportti health portal
allows the user to review the dosage of individual
substances, and also – within the various
pharmacotherapeutic groups – to compare the
safety of different drugs at different stages of renal
failure. The calculated glomerular filtration rate
(GFR) used for measuring renal function can be
determined by entering the patient’s plasma
creatinine level, age and height, if needed (when
GFR > 60 ml/min), and by selecting the appropriate
gender. The searches will then focus automatically
on the correct category of renal failure (Table 1).
Finnish Medical Journal 38/2010 vol. 65
Formulas for calculating
GFRs for the elderly
have not been
developed.
TABLE 1.
TABLE 1
In the Renbase database, the degree of renal
failure, based on glomerular filtration rate (GFR),
is divided into four categories according to the
classification of the European Medicines Agency
(EMA).
In the Renbase database, drug safety and the need for
dosage adjustment are described by a four-tier (A–D)
colour coding system.
GFR, ml/min
Degree of renal failure
A
80–50
50–30
30–10
< 10
mild
moderate
severe
end-stage renal failure;
dialysis patient
B1
C1
No need for adjustment of dosage or dose
interval
The information is missing or it has been
evaluated on the basis of the pharmacokinetic
characteristics of the drug
Adjustment of dosage or dose interval
D
The drug should not be used
1
For categories B and C, detailed evidence-based numerical
instructions are provided for adjusting the dosage.
The safety classification of the drugs has been
divided into four categories (Table 2). The
database uses a letter and colour coding
system similar to that of the SFINX interaction
database.
The user’s perspective
Using the database in Terveysportti health
portal is easy and quick. The classification is
clear and easy to understand, the
explanations are concise and therefore quick
to read. The calculated GFR can be
conveniently obtained on the same page
without the need for extra clicks. Renbase
should be used whenever the patient’s renal
function is not normal, or when a new drug
treatment is started for a patient over
65 years of age or the dosage is adjusted. It is
also helpful to check the database in case of
uncertainty concerning the need to take renal
function into consideration with a certain
drug or dose.
For a renal failure patient, the initial dose of
the drug is usually the same as the regular
treatment dose. For example, antibiotic
therapy should not be started with a low
maintenance dose adapted for renal failure;
instead, a regular dose should be used as a
loading dose to quickly achieve therapeutic
drug levels.
Finnish Medical Journal 38/2010 vol. 65
One should also keep in mind that advancing age
affects renal function, and the appropriateness of
the maintenance dose should thus be regularly
evaluated in long-term drug therapy. When a
patient is struck with an acute illness, the
impairment of renal function is usually taken into
account and the drug dose is reduced to match the
degree of renal failure. During convalescence,
however, checking and increasing the dose may be
forgotten – this presents the risk of therapy
becoming ineffective because the drug doses are
too low.
Maintenance doses for each degree of renal failure
are provided in the database. For example,
physicians sometimes hesitate to start digitalis
therapy for patients with renal failure, even when
the patient’s clinical condition clearly necessitates
it. This is an example of a situation where Renbase
supports decision-making. Also, anti-inflammatory
analgesics are sometimes prescribed for debilitated
elderly persons regardless of renal failure, while
ACE inhibitors and angiotensin receptor blockers
may be excluded even on insufficient grounds if the
patient’s plasma creatinine level has increased. The
database provides support for making these types
of treatment decisions.
Calculating the glomerular filtration rate
The Renbase database uses the Cockcroft-Gault
formula and the MDRD study equation for
determining the glomerular filtration rate. The
following values are entered in the Cockcroft-Gault
formula: the patient’s age (yrs), weight (kg), gender
and plasma creatinine level (µmol/l), in which case
GFR (ml/min) is (140 – age) x weight) / (a x P-CREA).
The coefficient is 0.8 for men and 0.95 for women.
Affiliations:
Maarit Wuorela has been a
presenter at events organised
by pharmaceutical companies
(Boehringer-Ingelheim, Sanofiaventis) and has participated
in conferences abroad at the
expense of pharmaceutical
companies (Baxter,
Boehringer-Ingelheim,
Novartis, Novo Nordisk,
Roche, Sanofi-aventis).
Tapio Kuitunen is Medical
Advisor at Algol Pharma Oy.
Arja Helin-Salmivaara: no
affiliations
The MDRD (Modification of Diet in Renal
Disease) study equation is a GFR assessment
method based on data acquired from
American adult renal patients. According to
the equation, GFR is
in men: 175 x (P-CREA/88.4)-1.154 x age-0.203 and
in women: 175 x (P-CREA/88.4)-1.154 x age-0.203 x 0.742
The patient’s weight is not needed here
because the result is expressed in a way
which is normalised as per the average adult
body surface area (1.73 m2).
The GFR calculator is constructed so that it
always uses the MDRD equation as a starting
point. If the MDRD equation estimates the
GFR to exceed 60 ml/min, the calculator asks
for the patient’s height, calculates the weight
corresponding to a body mass index of
25 kg/m2 and enters it automatically into the
Cockcroft-Gault formula. The correction has
the advantage of reducing the error caused
by significant overweight. The question arises,
however, if the Cockcroft-Gault formula
actually applies in this instance, since the
original formula specifically uses the subject’s
weight instead of a standard weight
calculated on the basis of height and based
on a certain BMI value. On the other hand,
the Cockcroft-Gault formula is only used in
mild renal failure (GFR > 60 ml/min), which
restricts the need for dose adjustment to a
very small number of drugs.
Using the calculated GFR does include several
sources of error, however. First of all, no GFR
calculation formulas have been developed for
the elderly population. A GFR value derived
from formulas is probably erroneous in the
case of sarcopaenic elderly persons with small
muscle mass. In practice, problems may also
be caused by the fact that the formula asks
for height instead of weight.
Finnish Medical Journal 38/2010 vol. 65
Measuring the height of a forgetful, debilitated
elderly person is not that easy. And – when
calculating the GFR of elderly persons – should the
maximum height in their youth be used (men, at
least, know how tall they were when they joined
the army), or should the 5–10 cm lost to age or
possibly osteoporosis be deducted? The question
applies to almost all elderly people.
Limitations
Stability is a prerequisite for using mathematical
GFR formulas: the plasma creatinine level must
reflect a state of equilibrium, and the patient’s
condition must be stable. However, mathematical
formulas cannot be used to calculate the
glomerular filtration rate of an acutely ill patient,
because urine secretion and renal function may
vary even on an hourly basis. For example, the GFR
of an oliguric patient is likely to be under 5 ml/min,
regardless of the plasma creatinine level at that
moment. In patients suffering from dehydration or
severe oedema, the distribution volume of drugs is
likely to vary. Would it be possible to include a
mention of this in the database, at least for drugs
whose dosage may be affected by it in practice?
Renal function is not merely a matter of glomerular
filtration. On the contrary, tubular secretion and
reabsorption have a significant impact on the
clearance of pharmaceutical substances. Even so,
calculated GFR is, to date, the most useful indicator
of renal function when assessing drug doses. As the
population ages and renal failure becomes more
common, we hope, however, that pharmacokinetic
studies will also be extended to this segment of the
population often excluded from clinical studies.